This invention relates to 3-(aminoethylidene)-7-oxo-4-oxaazabicyclo[3.2.0]heptane-2-carboxylic acid and its pharmaceutically acceptable salt, ester and amide derivatives which are useful as antibiotics. This invention also relates to processes for the preparation of such compounds; to pharmaceutical compositions comprising such compounds; and to methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.
The compounds of the present invention may be represented generically by the following structural formula (I): ##STR2## wherein X is oxygen, sulphur or NR.sup.1 (R.sup.1 is hydrogen or R); R is hydrogen or, inter alia, is representatively selected from the group consisting of the pharmaceutically acceptable salt, ester, anhydride and amide moieties known in the bicyclic .beta.-lactam antibiotic art--such moieties are enumerated representatively in greater detail below.
The compounds of the present invention, I, are related to the known antibiotic, 3-(.beta.-hydroxyethylidene)-7-oxo-4-oxaazabicyclo[3.2.0]heptane-2-carboxy lic acid which is also known as clavulanic acid (II): ##STR3## Clavulanic acid and its pharmaceutically acceptable salt and ester derivatives are fully disclosed, for example, in West German Patent Application (Offenlegungsschrift) No. 2,517,316 (1975). Clavulanic acid and its known salt and ester derivatives are useful starting materials for the preparation of the compounds of the present invention.
There is a continuing need for new antibiotics. For unfortunately, there is no static effectiveness of a given antibiotic because wide scale usage of any such antibiotic selectively gives rise to resistant strains of pathogens. In addition, the known antibiotics are effective only against certain types of microorganisms. Accordingly, the search for new antibiotics continues.
Unexpectedly, it has been found that the compounds of the present invention are broad spectrum antibiotics, which are useful in animal and human therapy and in inanimate systems.
Thus, it is an object of the present invention to provide the novel class of antibiotics depicted by structure I, above. These antibiotics are active against a broad range of pathogens which representatively include both gram positive bacteria such as S. aureus, S. pyogenes, and B. subtilis and gram negative bacteria such as E. coli., Proteus morganii, and Klebsiella. Further objects of this invention are to provide chemical processes for the preparation of such antibiotics and their non-toxic pharmaceutically acceptable salt, ester and amide derivatives; pharmaceutical compositions comprising such antibiotics; and to provide methods of treatment comprising administering such antibiotics and compositions when an antibiotic effect is indicated.